Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) wi ....Novel cellular functions of the microtubule-associated protein tau: Physiological and pathological implications. The social and economic burden of Alzheimer's disease (AD) is enormous, and by 2040 more than 500,000 Australians will suffer from this disease. A key histopathological hallmark of this and many other related diseases are insoluble deposits of the protein tau. Research into novel functions of tau in signalling and transport (both of which are heavily compromised in diseased brains) will be followed directly by assay development for tau-directed drug screening. The national benefit of this research is manifold by (a) patenting new data, (b) developing treatment strategies for an un-curable disease, and (c) establishing links to the growing Australian biotech industry (in addition to existing links to international pharmaceutical companies).Read moreRead less
The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciph ....The biological and pathological functions of TDP-43. The social and economic burden of neurodegenerative such as MND is enormous. A key histopathological hallmark of this and many other related diseases are deposits of the protein TDP-43. Our research aims at understanding its largely unknown functions, for example by generating transgenic animal models. These will form the base for the development for a TDP-43-directed drug treatment. The national benefit of this research is manifold: by deciphering basic biological mechanisms, patenting new data, developing treatment strategies for un-curable and fatal disorders, and expanding links to Australian biotech and international pharmaceutical companies.Read moreRead less
Neuronal functions of the microtubule-associated protein tau in development and ageing. The project uses a combination of transgenic mouse strains characterised by neurodegeneration and senescence-accelerated (SAM) mice, to determine the first steps of the aggregation of the protein tau in degenerating neurons, how absence of tau protects from brain atrophy, and in which physiological processes tau is involved. This project provides the biological foundation for a tau-based therapy of senescence ....Neuronal functions of the microtubule-associated protein tau in development and ageing. The project uses a combination of transgenic mouse strains characterised by neurodegeneration and senescence-accelerated (SAM) mice, to determine the first steps of the aggregation of the protein tau in degenerating neurons, how absence of tau protects from brain atrophy, and in which physiological processes tau is involved. This project provides the biological foundation for a tau-based therapy of senescence-associated conditions. It provides the biological foundation for developing effective therapies for human neurodegenerative conditions, by preventing tau aggregation and phosphorylation. We will patent new data and expand our existing links to Australian biotech and international pharmaceutical companies.Read moreRead less
Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. ....Do pancreatic stellate cells play a role in pancreatic exocrine secretion? 3 major national benefits: 1)Alignment with research priority goals of preventative health care and ageing well ageing productively. Elucidation of mechanisms of action of CCK and the interaction of PSCs and acinar cells in mediating pancreatic secretion will help refine our approach to the prevention and treatment of disorders related to the above processes viz. maldigestion, malabsorption, obesity and pancreatic cancer. 2)Enhancement of Australia's reputation in gastrointestinal (GI) research through a unique collaboration between internationally recognised researchers in GI and pancreatic biology. 3)Training opportunities for Australian research students and scientists in physiology, gastroenterology and pancreatology.Read moreRead less
Nuclear Trafficking of Apolipoprotein-E. Apolipoprotein-E (apoE) regulates specific age-related neurodegenerative and cardiovascular diseases. The role of apoE in these disorders is unclear. This project will benefit our community by providing the basic cell biology knowledge required to understand disease mechanisms and ultimately provide avenues for better treatments. Aspects of the project will focus on the modification of apoE by carbohydrates and the interaction of apoE with cellular carboh ....Nuclear Trafficking of Apolipoprotein-E. Apolipoprotein-E (apoE) regulates specific age-related neurodegenerative and cardiovascular diseases. The role of apoE in these disorders is unclear. This project will benefit our community by providing the basic cell biology knowledge required to understand disease mechanisms and ultimately provide avenues for better treatments. Aspects of the project will focus on the modification of apoE by carbohydrates and the interaction of apoE with cellular carbohydrate-containing structures. The importance of carbohydrates in the regulation of cellular and protein function is increasingly recognised and forms a foundation for the rapidly expanding discipline of glycobiology. This project will strengthen Australia's glycobiology research capacity.Read moreRead less
Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical int ....Role of autophagy in degradation of endoplasmic reticulum (ER)-localised protein aggregates. This study will provide a new understanding of protein aggregate accumulation in the endoplasmic reticulum (ER), a phenomenon that occurs in aging cells and protein conformational diseases, and under stress conditions and during secretory protein overexpression. This information will inform strategies to prevent the onset of protein conformational diseases and help identify targets for pharmaceutical intervention. In addition, a powerful model system for studies of ER protein aggregation will be established, high-level training in biochemistry and morphometry will be provided, and an international collaboration of the highest calibre will be initiated.Read moreRead less
Characterisation of APC intracellular trafficking pathways. This is a fundamental research project aimed at addressing the cell biology of the APC tumour suppressor protein. APC gene mutations are directly linked to the development of colorectal cancer, a serious healthcare issue in Australia with approximately 12,400 new cases diagnosed each year and around 4,700 deaths. The severity of cases in men and women who develop colorectal cancer makes this a socio-economically serious health issue, an ....Characterisation of APC intracellular trafficking pathways. This is a fundamental research project aimed at addressing the cell biology of the APC tumour suppressor protein. APC gene mutations are directly linked to the development of colorectal cancer, a serious healthcare issue in Australia with approximately 12,400 new cases diagnosed each year and around 4,700 deaths. The severity of cases in men and women who develop colorectal cancer makes this a socio-economically serious health issue, and our project falls within the Research Priority 2: Promoting and Maintaining Good Health. If successful our project will identify localisation patterns and pathways of movement of APC within cells, which could ultimately help in development of treatments. Read moreRead less